Transglutaminase is a calcium and thiol dependent enzyme which is found in a number of organs and tissues (epidermis, hair follicles, liver, blood, etc.) and which is responsible for the crosslinking of proteins by the formation of covalent bonds between lysine and glutamine residues. Transglutaminase has a high specificity for protein-bound glutamine residues and a low specificity for lysine. A variety of amines have been reported as substrates for transglutaminase, including dansylcadaverine, methyl amine, butyl amine, histamine and putrescine and hydroxylamine. Hydroxylamine is in fact the amine donor in a standard assay for transglutaminase activity wherein hydroxylamine is covalently bound to an N-terminal blocked peptide containing glutamine and glycine to produce hydroxamate, which is detected by color formation in the presence of ferric chloride and acid. One Unit of transglutaminase is defined as that amount which will form 1 .mu.Mole of hydroxamate per minute at 37.degree. C.
It is also known that the fluorescent primary amine dansylcadaverine can be introduced to a variety of protein substrates via transglutaminase. These include fibrin, casein and B-lactoglobulin, cold insoluble globulin, alpha.sub.2 -macroglobulin, erythrocyte ghosts and proteins in sarcoplasmic reticulum, myosin and actin, rhodopsin, and guinea pig liver transglutaminase itself.
Lorand et al., "The specificity of guinea pig liver transglutaminase for amine substrates," Biochem. 18, 1756-1765 (1979), discloses the specificity of guinea pig liver transglutaminase for synthetic primary amines having high apparent affinities for transglutaminase. These studies revealed that optimal transglutaminase activity was achieved when compounds had (a) alkylamine side-chain lengths equivalent to 5 methylene groups (or 7.2-7.6 A long), (b) no branching nor groups bulkier than methylene along the alkyl amine chain and (c) hydrophobic moieties attached to the alkyl chain.
Japanese patent application 3213574 discloses the use of transglutaminase to cross-link the amino acid functional groups of the cuticle part of the animal hair in order to produce hair or hair fiber containing materials having good shrinkage resistance, pill resistance, and hydrophobic property. Japanese patent application 3095109 and Japanese patent application 3083908 disclose hair or skin cosmetic material containing transglutaminase modified with a water-soluble substance, e.g., polyethyleneglycol, ethyleneglycol, propyleneglycol, glycerine, PVA, glucose, sucrose, fructose, alginic acid, CMC, starch and hydroxypropylcellulose. Japanese patent application 3038511 discloses cosmetic compositions containing transglutaminase. The compositions are said to give a good conditioning effect. Japanese patent applications 2204407 and Japanese patent application 2169511 disclose hair and skin cosmetic materials containing transglutaminase and water-soluble polyhydride alcohol and optionally calcium salt. The Japanese patent applications disclose the repair of damaged skin or hair surfaces by the action of transglutaminase upon cuticle or stratum corneum. Transglutaminase itself is the active ingredient in the disclosed compositions. None of the above-referenced Japanese patent applications describe the use of transglutaminase in conjunction with an active agent containing an alkylamine moiety.
It is an object of the present invention to provide a composition for delivery of an active ingredient to human skin, hair, or nails.
It is another object of the present invention to provide a composition for topical application to human skin, hair, or nails, which composition contains transglutaminase and an active ingredient including an alkylamine moiety.
These and other objects of the invention will become more apparent from the detailed description and examples that follow.